The present invention is directed to oxazolidinones, oxazolidinone compositions, and methods for their preparation and use.
Oxazolidinones are compounds where an amine group and a hydroxyl group on adjacent carbon atoms have been cyclized to form a 5-membered ring containing a carbonyl group. Certain oxazolidinones have been shown to exhibit a variety of biological activities. For example, some oxazolidinones are inhibitors of monoamine oxidase-B, an enzyme implicated in Parkinson""s disease. See, for example, Ding et al., J. Med. Chem. 36:3606-3610 (1993).
Scientists have reported that certain oxazolidinone derivatives exhibit beneficial antibacterial effects. For instance, N-[3-[3-fluoro-4-(morpholin-4-yl)phenyl]2-oxooxazolidin-5(s)-ylmethyl]acetamide (below) has been reported to be useful for the treatment of bacterial infections. Lizondo et al., Drugs of the Future, 21:1116-1123 (1996).
A ten step synthesis of oxazolidinone antibiotics has been described. U.S. Pat. No. 5,547,950. A four step synthesis of the antibacterial compound U-100592 also has been reported. Schauss et al., Tetrahedron Letters, 37:7937-7940 (1996). A five step preparation of enantiomerically pure cis- and trans-N-(propionyl)hexahydrobenzoxazolidin-2-ones further was reported. De Parrodi et al., Tetrahedron: Asymmetry, 8:1075-1082 (1997). 
The synthesis of the oxazolidinone antibacterial agent shown below has been reported. Wang et al., Tetrahedron, 45:1323-1326 (1989). This oxazolidinone was made using a process that included the reaction of an aniline with glycidol to provide an amino alcohol, and the diethylcarbonate mediated cyclization of the amino alcohol to afford an oxazolidinone. 
The synthesis of oxazolidinone antibacterial agents, including the compound shown below has been reported. U.S. Pat. No. 4,705,799. The process used to make the compound shown below included a metal mediated reduction of a sulfonyl chloride to provide a sulfide. 
The synthesis of oxazolidinone antibacterial agents, including the pyridyl compound shown below has been reported. U.S. Pat. No. 4,948,801. The process used included an organometallic mediated coupling of an organotin compound and an aryl iodide. 
Other reports of syntheses of oxazolidinone compounds are described in DE 196 01 264 A1, EP 0 789 026 A1, DE 196 04 223 A1, EP 0 738 726 A1, and PCT WO 98/54161.
The synthesis of oxazolidinone compounds also is described in U.S. patent application Ser. No. 09/012,535, filed Jan. 23, 1998, U.S. patent application Ser. No. 09/086,702, filed May 28, 1998, U.S. patent application Ser. No. 09/235,771, filed Jan. 22, 1999, and PCT/US99/01318, filed Jan. 22, 1999, the disclosures of which are incorporated herein by reference in their entirety.
Provided are oxazolidinones, compositions comprising oxazolidinones, as well as methods of their synthesis and use. Also provided are compositions for the treatment or prevention of an infectious disorder comprising an effective amount of any oxazolidinone compound disclosed herein and a pharmaceutically acceptable carrier. Methods are provided of treating or preventing an infectious disorder in a human or other animal subject, comprising administering to the subject an effective amount of any oxazolidinone compound disclosed herein.